**10. Antibacterial photodynamic therapy in combination with chemotherapy**

The urgent response to the fast development of bacterial resistance to antibiotics is probably the single most compelling reason for the current rising interest in nanomaterial-mediated PDT, specifically the ability of nanomaterials to carry multiple drug and PS payloads and to deliver them only in the infection site or upon stimulation by an external source, which is the basis for combination therapies involving PDT. The reason for this is that although mechanisms of resistance against antibacterial PDT have been described, including hypoxia, the repair of DNA damage, efflux of the PS, upregulation of the heat shock protein, and inhibition of apoptosis [97], very little resistance has been observed [98–100]. Antibiotic therapy and PDT have been the subject of much interest [101–104].

Incorporating a porphyrin PS, the immunosuppressant methotrexate, and silver in one nanoconjugate may be used as an example of the nanomaterial-mediated combination of PDT with an antibiotic material [105]. While demonstrating biocompatibility and release of silver and the porphyrin PS, the nanoconjugate also showed excellent antibacterial activity in excess of that shown by the antibiotic and the porphyrin PS each acting alone. This type of combination of antibiotic silver with PDT was also shown by the eradication of *S. aureus* by a conjugate of the zinc (II) phthalocyanine PS with silver NPs [106]. Another example is the PDT treatment with amoxicillin-coated gold NPs, eradicating the embedded *P. aeruginosa* and *S. aureus*. In this example, amoxicillin was the antibiotic agent, while the nanogold acted as the PS [107]. Similarly, the biofilms of *E. coli*, *S. aureus*, and MRSA were treated with an MOF loaded with the PS methylbenzene blue and the antibiotic drug vancomycin [108]. This caused the biofilm matrix structure to collapse. The nanoconjugate was therefore able to diffuse and eradicate the bacteria. This is an example of a pHtriggered release of the antibiotic and the PS because the MOF structure disassembles upon the drop in pH as the nanoconjugate enters the bacterial and biofilm infection site and as it enters the bacterial cell into the cytoplasm.

## **11. Anticancer photodynamic therapy in combination with chemotherapy**

Given the history of PDT and chemotherapy as anticancer therapeutic technologies, it is not surprising that the combination of PDT and anticancer chemotherapy is among the most widely reported. A study of the combination of the aluminum phthalocyanine chloride complex as the PS and doxorubicin as the chemotherapy drug agent, both encapsulated in nano-emulsions, was reported to reduce the induction of breast cancer in mice, to reduce the expression of the vascular endothelial growth factor, and to increase the expression of the apoptosis-indicating Caspase-3 protein as well as tissue death by necrosis. There was a large reduction in cancer cell proliferation [109]. The combination of PDT with anticancer chemotherapy was also studied using chlorin-e6 as the PS and cisplatin as the chemotherapy drug while ameliorating hypoxia using perfluorocarbon-mediated molecular oxygen self-supply. These three key elements were incorporated in pH- and ROS-responsive micelles made of polyethylene glycol and polyglycolic acid. This remarkable innovation showed enhanced activity against SKOV3 ovarian cancer cell lines [110]. This was attributed to the pH responsiveness, which ensured that the nano-micelles released their cargo only when they were inside the ovarian cancer cells. The perfluoro hydrocarbon-mediated oxygen encapsulation in the micelles ensured oxygenation to overcome hypoxia. **Figure 11** shows a similar nanoconjugate formed by the self-assembly of polyethylene glycol

*Important Advances in Antibacterial Nanoparticle-Mediated Photodynamic Therapy DOI: http://dx.doi.org/10.5772/intechopen.113340*

#### **Figure 11.**

*Self-assembly of polyethylene glycol after conjugation with the perfluoro hydrocarbon and IR780 was loaded with doxorubicin.*

after conjugation of the PS IR780 with a perfluoro hydrocarbon, along with loading with doxorubicin, achieving similar results against MCF-7 cancer cell lines [111].
